Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01100437
Previous Study | Return to List | Next Study

Safety Study to Assess Opiate Withdrawal Signs and Symptoms in Opioid Dependent Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01100437
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : April 9, 2010
Results First Posted : March 28, 2012
Last Update Posted : July 13, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE April 7, 2010
First Posted Date  ICMJE April 9, 2010
Results First Submitted Date  ICMJE February 27, 2012
Results First Posted Date  ICMJE March 28, 2012
Last Update Posted Date July 13, 2012
Study Start Date  ICMJE April 2010
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2012)
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Greater Than or Equal to (≥) 13 in the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24 hours (hr) post-dose and unscheduled assessment (UA) ]
COWS is an 11 section clinical assessment of withdrawal symptoms, each section is rated from 0 (no symptom) to 4 or 5 (most severe symptom). Total score is classified into a 4 point rating scale (mild 5-12, moderate 13-24, moderately severe 25-36 and severe more than 36 points).
Original Primary Outcome Measures  ICMJE
 (submitted: April 7, 2010)
Number of patients with Clinical Opiate Withdrawal Scale (COWS) score ≥ 13 in the Treatment Phase [ Time Frame: within 24 hours post dosing ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
  • Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases [ Time Frame: Baseline up to Day 63 ]
    Average pain scores in the previous 24 hours using an 11 point NPRS ranging from no pain (0) to worst pain (10).
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average Tmax for Morphine, Naltrexone and 6-β-Naltrexol
  • Maximum Observed Plasma Concentration (Cmax) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average Cmax for Morphine, Naltrexone and 6-β-Naltrexol
  • Minimum Observed Plasma Concentration (Cmin) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average Cmin for Morphine, Naltrexone and 6-β-Naltrexol
  • Apparent Oral Clearance (CL/F) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Volume of Distribution (Vd/F)During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average Vd/F for Morphine, Naltrexone and 6-β-Naltrexol
  • Plasma Decay Half-Life (t1/2) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average plasma decay half-life of morphine, naltrexone and 6-β-Naltrexol. Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-τ) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average AUC0-τ for Morphine, Naltrexone and 6-β-Naltrexol reported. τ=24 hours
  • Area Under the Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    Average AUC0-last for Morphine, Naltrexone and 6-β-Naltrexol. Area under the plasma concentration time-curve from time zero to the last measured concentration.
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). Average AUC 0-∞ for Morphine, Naltrexone and 6-β-Naltrexol reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2010)
  • Mean maximum COWS score in the Treatment Phase [ Time Frame: within 24 hours post dosing ]
  • Mean morphine plasma concentration at first occurrence of COWS ≥ 13 in the Treatment Phase. [ Time Frame: within 24 hours post dosing ]
  • Mean naltrexone plasma concentration at first occurrence of COWS ≥ 13 in the Treatment Phase. [ Time Frame: within 24 hours post dosing ]
  • Mean 6-β-naltrexone plasma concentration at first occurrence of COWS ≥ 13 in the Treatment Phase. [ Time Frame: within 24 hours post dosing ]
Current Other Pre-specified Outcome Measures
 (submitted: February 27, 2012)
  • Time to First Occurrence of a COWS Score ≥ 13 for Each Treatment During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24 hr post-dose and UA ]
    Average time to first occurrence of a COWS score ≥ 13
  • Morphine Plasma Concentration at First COWS ≥ 13 in the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
  • Naltrexone Plasma Concentration at First COWS ≥ 13 in the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
  • 6-β-Naltrexone Plasma Concentration at First COWS ≥ 13 in Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ]
  • Maximum Post-dose COWS in the Treatment Phase [ Time Frame: Between 0.5 and 24 hours post-dose ]
    COWS is an 11 section clinical assessment of withdrawal symptoms, each section is rated from 0 (no symptom) to 4 or 5 (most severe symptom). Total score is classified into a 4 point rating scale (mild 5-12, moderate 13-24, moderately severe 25-36 and severe more than 36 points).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study to Assess Opiate Withdrawal Signs and Symptoms in Opioid Dependent Patients
Official Title  ICMJE A Single-Center, Randomized, Double-Blind, Two-Way Crossover Study to Evaluate Whether a Single-Dose Administration of Crushed and Whole EMBEDA Induces Clinical Opiate Withdrawal Signs and Symptoms in Opioid-Dependent Patients With Chronic, Non-Cancer Pain Who Are Stabilized on EMBEDA¿
Brief Summary This study will evaluate whether crushed EMBEDA capsules induce clinical opiate withdrawal signs and symptoms in opioid-dependent patients with chronic non-cancer pain who are stabilized on EMBEDA.
Detailed Description The decision to terminate the trial was due to a lack of study drug supply. Decision was not based on any safety concerns. The date of the notification of termination letter was March 11, 2011.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Condition  ICMJE Chronic Pain
Intervention  ICMJE
  • Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush
    Placebo capsules plus EMBEDA capsules crushed and mixed in solution administered orally at each patient's stable dose, given either once daily or twice daily
  • Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
    EMBEDA capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily with 150mL placebo solution
Study Arms  ICMJE
  • Experimental: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush
    EMBEDA (morphine sulfate plus naltrexone hydrochloride ER) capsules crushed and mixed in solution and administered orally at each patient's stable dose, given either once daily or twice daily.
    Intervention: Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush
  • Experimental: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
    EMBEDA (morphine sulfate plus naltrexone hydrochloride ER) capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily
    Intervention: Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
Publications * Setnik B, Roland CL, Goli V, Sommerville K, Webster L. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients. J Opioid Manag. 2013 Mar-Apr;9(2):139-50. doi: 10.5055/jom.2013.0155.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 29, 2011)
14
Original Estimated Enrollment  ICMJE
 (submitted: April 7, 2010)
80
Actual Study Completion Date  ICMJE March 2011
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Chronic moderate to severe non-cancer pain that has been treated with opioid analgesics for at least three months (with stabilized pain control and stabilized dose for 28 days prior to enrollment).
  • Receiving an opioid dose equivalent to 20 mg - 120 mg morphine once or twice daily.
  • Patient displays signs and symptoms of withdrawal (i.e., COWS score ≥5) following naloxone administration during the Naloxone Challenge.

If female and able to become pregnant, must use an approved method of birth control.

  • Excluding the chronic moderate to severe non-cancer pain, the patient is judged by the Investigator to be in generally good health at screening based upon the results of a medical history, physical examination, laboratory profile, and 12 lead electrocardiogram (ECG).

Exclusion Criteria:

  • Female who is pregnant or breastfeeding.
  • Patient has a known allergy or history of significant adverse reaction to morphine, other opioids, naltrexone, acetaminophen, or related compounds.
  • Patient is receiving systemic chemotherapy, has an active malignancy of any type, or has been diagnosed with cancer within the 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin).
  • History of, or ongoing, alcohol or drug abuse.
  • Patient has made a donation of blood or has had a significant blood loss within 30 days prior to screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01100437
Other Study ID Numbers  ICMJE ALO-01-09-111
B4541002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP